This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyperpolarized helium-3 magnetic resonance imaging (HP 3He MRI) has been extensively used for quantitative assessment of lung structure and function on a regional basis. Alveolar size airway morphology at the small spatial scales can be elucidated using HP 3He MR apparent diffusion coefficient (ADC) imaging. Specific techniques have also been developed for measurement of pulmonary oxygen tension (PAO2) and uptake (ODR). Previous work in this area led to a multiple-regression-based single acquisition technique for simultaneous measurement of PAO2 and ODR. This technique is now expanded for simultaneous measurement of PAO2, ODR and 3He ADC. This approach is of special significance in human by allowing for correlated measurements of lung function and structure. Moreover, it allows for all three quantities to be measured in one single breath-hold, rather than in two breaths, which decreases both the scan time and the required amount of HP 3He gas. These factors facilitate repeated measurements of lung oxygenation and gas diffusion in large-scale human trials and future clinical applications.